Membrane‐Based Approach for the Downstream Processing of Influenza Virus‐Like Particles

2019 ◽  
Vol 14 (8) ◽  
pp. 1800570 ◽  
Author(s):  
Sofia B. Carvalho ◽  
Ricardo J. S. Silva ◽  
Mafalda G. Moleirinho ◽  
Bárbara Cunha ◽  
Ana S. Moreira ◽  
...  
2019 ◽  
Vol 164 ◽  
pp. 12-22 ◽  
Author(s):  
Jo-Yu Hong ◽  
Ting-Hsuan Chen ◽  
Yu-Jou Chen ◽  
Chia-Chyi Liu ◽  
Jia-Tsrong Jan ◽  
...  

2008 ◽  
Vol 6 (9) ◽  
pp. 930-940 ◽  
Author(s):  
Marc-André D’Aoust ◽  
Pierre-Olivier Lavoie ◽  
Manon M.-J. Couture ◽  
Sonia Trépanier ◽  
Jean-Martin Guay ◽  
...  

2019 ◽  
Vol 234 (9) ◽  
pp. 16643-16652 ◽  
Author(s):  
Mohsen Keshavarz ◽  
Haideh Namdari ◽  
Yaser Arjeini ◽  
Hamed Mirzaei ◽  
Vahid Salimi ◽  
...  

2010 ◽  
Vol 84 (9) ◽  
pp. 4673-4681 ◽  
Author(s):  
Dan Wang ◽  
Aaron Harmon ◽  
Jing Jin ◽  
David H. Francis ◽  
Jane Christopher-Hennings ◽  
...  

ABSTRACT The matrix protein (M1) of influenza A virus is generally viewed as a key orchestrator in the release of influenza virions from the plasma membrane during infection. In contrast to this model, recent studies have indicated that influenza virus requires expression of the envelope proteins for budding of intracellular M1 into virus particles. Here we explored the mechanisms that control M1 budding. Similarly to previous studies, we found that M1 by itself fails to form virus-like-particles (VLPs). We further demonstrated that M1, in the absence of other viral proteins, was preferentially targeted to the nucleus/perinuclear region rather than to the plasma membrane, where influenza virions bud. Remarkably, we showed that a 10-residue membrane targeting peptide from either the Fyn or Lck oncoprotein appended to M1 at the N terminus redirected M1 to the plasma membrane and allowed M1 particle budding without additional viral envelope proteins. To further identify a functional link between plasma membrane targeting and VLP formation, we took advantage of the fact that M1 can interact with M2, unless the cytoplasmic tail is absent. Notably, native M2 but not mutant M2 effectively targeted M1 to the plasma membrane and produced extracellular M1 VLPs. Our results suggest that influenza virus M1 may not possess an inherent membrane targeting signal. Thus, the lack of efficient plasma membrane targeting is responsible for the failure of M1 in budding. This study highlights the fact that interactions of M1 with viral envelope proteins are essential to direct M1 to the plasma membrane for influenza virus particle release.


Vaccine ◽  
2010 ◽  
Vol 28 (37) ◽  
pp. 6104-6113 ◽  
Author(s):  
Marc Pearton ◽  
Sang-Moo Kang ◽  
Jae-Min Song ◽  
Yeu-Chun Kim ◽  
Fu-Shi Quan ◽  
...  

2009 ◽  
Vol 83 (11) ◽  
pp. 5726-5734 ◽  
Author(s):  
Lucy A. Perrone ◽  
Attiya Ahmad ◽  
Vic Veguilla ◽  
Xiuhua Lu ◽  
Gale Smith ◽  
...  

ABSTRACT Influenza vaccines capable of inducing cross-reactive or heterotypic immunity could be an important first line of prevention against a novel subtype virus. Influenza virus-like particles (VLPs) displaying functional viral proteins are effective vaccines against replication-competent homologous virus, but their ability to induce heterotypic immunity has not been adequately tested. To measure VLP vaccine efficacy against a known influenza pandemic virus, recombinant VLPs were generated from structural proteins of the 1918 H1N1 virus. Mucosal and traditional parenteral administrations of H1N1 VLPs were compared for the ability to protect against the reconstructed 1918 virus and a highly pathogenic avian H5N1 virus isolated from a fatal human case. Mice that received two intranasal immunizations of H1N1 VLPs were largely protected against a lethal challenge with both the 1918 virus and the H5N1 virus. In contrast, mice that received two intramuscular immunizations of 1918 VLPs were only protected against a homologous virus challenge. Mucosal vaccination of mice with 1918 VLPs induced higher levels of cross-reactive immunoglobulin G (IgG) and IgA antibodies than did parenteral vaccination. Similarly, ferrets mucosally vaccinated with 1918 VLPs completely survived a lethal challenge with the H5N1 virus, while only a 50% survival rate was observed in parenterally vaccinated animals. These results suggest a strategy of VLP vaccination against a pandemic virus and one that stimulates heterotypic immunity against an influenza virus strain with threatening pandemic potential.


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